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Elevated lipoprotein(a)
Also known as Lipoprotein(a) · High lipoprotein(a) · Raised lipoprotein(a) · High Lp(a)
Lipoprotein(a), or Lp(a), is a cholesterol-carrying particle whose blood level is roughly 70-90% determined by your genes. Unlike most traits, a single gene region (LPA) accounts for much of this, but the precise level reflects the combined effect of the LPA kringle repeat and other common variants. Levels are largely set for life, so a high reading signals an inherited, independent risk of heart disease and stroke.
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Overview
Lipoprotein(a) is a low-density-lipoprotein-like particle carried in the blood. A high level is one of the most common inherited risk factors for cardiovascular disease, and crucially it acts independently of, and on top of, ordinary cholesterol, blood pressure and lifestyle. Around 1 in 5 adults worldwide, including in the UK, have a raised level (commonly defined as 125 nmol/L or above, roughly 50 mg/dL). Levels are largely fixed from early life and change little with diet, exercise or current medicines. Elevated Lp(a) usually causes no symptoms, so most people are unaware they carry the risk until a heart attack, stroke or narrowing of the aortic valve occurs, often at a younger age than expected. Levels differ by ancestry, tending to be highest in people of African heritage and intermediate in South Asian populations, which matters for interpreting any single threshold.
Symptoms & clinical features
Elevated lipoprotein(a) produces no symptoms of its own. It is a silent, lifelong risk factor: you cannot feel a high level, and it is detected only by a blood test. Its effect is to accelerate the diseases it contributes to. Over time, a high level promotes furring and hardening of the arteries (atherosclerosis), increasing the risk of angina, heart attack, ischaemic stroke and peripheral arterial disease, and it is also linked to narrowing and calcification of the aortic valve (aortic stenosis). When these conditions develop, they present in the usual way, for example chest pain on exertion, breathlessness or sudden stroke symptoms. Importantly, carrying a high polygenic or genetic Lp(a) risk does not change how these conditions look or feel; it changes how likely and how early they are.
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Affected organs
Elevated Lp(a) acts on the cardiovascular system. It chiefly affects the arteries, where it accelerates atherosclerosis in the coronary arteries supplying the heart, the carotid and cerebral arteries supplying the brain, and the peripheral arteries of the legs. It also affects the heart valves, being linked to calcification and narrowing of the aortic valve. The heart muscle itself is affected indirectly, through the consequences of reduced blood supply.
Risks & severity
A polygenic risk score is usually expressed as a percentile, showing where you sit relative to others, often paired with a relative risk such as how many times more likely a high-scoring person is to have a raised Lp(a) level or an earlier cardiovascular event. It describes probability across a population, not certainty for you: many people with a high score stay well, and some with a low score still develop heart disease through other causes. Predictive performance varies by condition and, importantly, by ancestry, because most scores were built largely in European-ancestry datasets and tend to be less accurate in people of other backgrounds. For Lp(a), genetics is unusually informative, but a score should still prompt a confirmatory blood test rather than stand alone.
Genetic causes
Lp(a) is one of the most strongly genetically determined cardiovascular traits, with heritability estimates of roughly 0.7-0.9. The single LPA gene on chromosome 6 dominates: it encodes apolipoprotein(a), and a copy-number variable region called the kringle IV type 2 (KIV-2) repeat largely sets particle size and concentration, with fewer repeats generally meaning higher levels. On top of this, several common single-letter variants independently raise levels, the best established being rs10455872 and rs3798220 in and around LPA, alongside others such as rs7770628, rs73596816 and rs6926458. Genome-wide studies also implicate modifier loci including APOE, where the ε2 allele is associated with lower Lp(a). A polygenic score combines the LPA repeat and these many common variants into a single estimate of inherited Lp(a)-related risk, capturing more of the picture than any one variant alone and explaining a large share of person-to-person variation.
Inheritance pattern
Elevated Lp(a) does not follow simple Mendelian inheritance. Although one gene region (LPA) carries most of the weight, your actual level is set by the combination of the kringle repeat length you inherit plus many smaller common variants from both parents. The result is a continuous spread across the population, from very low to very high, rather than neat categories of affected and unaffected. You inherit your genetic make-up from both parents, so a high level often clusters in families, and children of a parent with very high Lp(a) are more likely, but not certain, to have raised levels too. Because the contributing variants are common, a high level can also appear without any obvious family history, simply through an unlucky combination inherited from both sides.
Diagnosis & testing
A polygenic risk score for Lp(a) is an estimate of inherited risk, not a diagnosis and not a measurement of your actual Lp(a) level. It is calculated from a saliva or blood DNA sample by tallying the many common variants you carry, weighting each by its known effect and summarising the total as a percentile compared with a reference population. A high score means your genes predispose you to a raised Lp(a) level and the associated cardiovascular risk; it cannot tell you whether disease is present. The definitive next step is a simple, low-cost Lp(a) blood test, ideally measured in nmol/L, which gives your true concentration. Because levels are largely fixed for life, a single lifetime measurement is usually sufficient to confirm the genetic prediction.
Management & lifestyle
There is currently no licensed medicine that specifically lowers Lp(a), and routine lifestyle change has little effect on the level itself, so management focuses on confirming the level and aggressively reducing every other modifiable cardiovascular risk factor. People at elevated polygenic or measured risk should aim for tight control of LDL cholesterol, usually with statins and, where needed, additional lipid-lowering drugs; well-controlled blood pressure; not smoking; a healthy weight; and good management of diabetes. Knowing about a high level earlier supports more intensive primary prevention and a lower personal LDL target. In the UK, those with very high Lp(a) and progressive disease may be referred to a specialist lipid clinic, and lipoprotein apheresis is available in a small number of NHS centres for selected high-risk patients. Several targeted Lp(a)-lowering therapies are in late-stage trials.
UK care pathway
On the NHS, Lp(a) is not yet part of routine cardiovascular screening, and availability of the test varies between areas. UK guidance, including the HEART UK consensus, recommends measuring Lp(a) at least once in a lifetime, particularly in people with a personal or family history of premature heart disease, with familial hypercholesterolaemia, or with otherwise unexplained cardiovascular risk. Testing and ongoing management are usually arranged through a GP or, for complex cases, a specialist NHS lipid clinic, where overall cardiovascular risk is assessed and other risk factors are treated.
Frequently asked questions
How is polygenic Lp(a) risk different from a single faulty gene?
A single-gene (Mendelian) condition is caused by one specific fault that, on its own, usually causes the condition. Elevated Lp(a) is different: even though the LPA gene region carries most of the influence, your actual level is set by a combination of the inherited kringle repeat plus many common variants from both parents. A polygenic score adds these up to estimate risk along a continuous scale, rather than giving a yes-or-no genetic diagnosis.
Can I get an Lp(a) test on the NHS?
It is possible but not yet routine, and availability varies by area. UK guidance recommends measuring Lp(a) at least once in a lifetime, especially if you have a personal or family history of early heart disease or have familial hypercholesterolaemia. Ask your GP; complex cases may be referred to a specialist NHS lipid clinic. A polygenic score is not a substitute for this simple blood test, which measures your actual level.
If my Lp(a) is high, can I lower it with diet or exercise?
Your Lp(a) level is largely fixed by your genes and changes very little with diet, exercise or weight loss, and no licensed medicine yet specifically lowers it. What you can do is powerful: reduce every other risk factor. That means controlling LDL cholesterol (often with statins), keeping blood pressure healthy, not smoking and managing diabetes, which lowers your overall risk of heart attack and stroke.
Does a high polygenic score mean I will definitely get heart disease?
No. A polygenic score estimates probability, not certainty. A high score means you are more likely than average to have a raised Lp(a) level and earlier cardiovascular disease, but many high-scoring people stay well, and some with low scores still develop heart problems for other reasons. Scores are also less accurate in non-European ancestries. Treat a high score as a prompt to confirm with a blood test and to manage your overall risk.
References
- Nordestgaard BG, Langsted A. Lipoprotein(a) and cardiovascular disease. Lancet (London, England). 2024. PMID: 39278229
- Tsimikas S. A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies. Journal of the American College of Cardiology. 2017. PMID: 28183512
- Kamstrup PR. Lipoprotein(a) and Cardiovascular Disease. Clinical chemistry. 2021. PMID: 33236085
- Blumenthal RS, Morris PB, Gaudino M. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2026. PMID: 41824590
- Parhofer KG, Laufs U. Lipid Profile and Lipoprotein(a) Testing. Deutsches Arzteblatt international. 2023. PMID: 37403458
- Reyes-Soffer G, Yeang C, Michos ED. High lipoprotein(a): Actionable strategies for risk assessment and mitigation. American journal of preventive cardiology. 2024. PMID: 38646021
- Anchouche K, Baass A, Thanassoulis G. Lp(a): A Clinical Review. Clinical biochemistry. 2025. PMID: 40258460
- Volgman AS, Koschinsky ML, Mehta A. Genetics and Pathophysiological Mechanisms of Lipoprotein(a)-Associated Cardiovascular Risk. Journal of the American Heart Association. 2024. PMID: 38879448